An n-amino-alpha-amino acid compound and a method for synthesizing the same

Abstract

The application provides an N-amino-alpha-amino acid compound and a synthesis method thereof, and the synthesis method is as follows: hydrazone reaction substrates, a photocatalyst, a reducing agent and alkali are added into a reaction container, then organic solvents are added under a CO2 atmosphere, stirring reaction is carried out under light conditions at 20-70 DEG C for 0.1-48 h, and then the reaction product is separated and purified to obtain the N-amino-alpha-amino acid compound; the synthesis method can synthesize important N-amino-alpha-amino acid compounds under mild reaction conditions, has the characteristics of wide reaction substrate range, good yield and good regioselectivity, cheap and easily obtained raw materials and easily derivable products, and can effectively solve the problems of limitations and the need to use metal reducing agents in the synthesis of alpha-aryl-substituted alpha-amino acid products in the prior art.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of organic synthesis, and particularly relates to an N-amino-alpha-amino acid compound and a synthesis method thereof. BACKGROUND

[0002] Alpha-amino acid is an important compound and a basic unit of polypeptide and protein. There are only 20 kinds of well-known natural alpha-amino acids, and the preparation thereof can be realized by microbial fermentation. Since there are only amino, carboxyl, sulfhydryl and other modifiable groups in the structure of natural alpha-amino acid, it is challenging to realize the structural diversification thereof. On the other hand, non-natural amino acid structural units exist widely in the synthesis precursors of some natural products, biologically active molecules and drug molecules. Therefore, it is of great significance to synthesize non-natural amino acids with diverse structures.

[0003] On the other hand, carbon dioxide (CO2) is a cheap, safe, non-toxic and abundant carbon resource, and it is of great significance to make it undergo chemical transformation to synthesize high-value-added chemicals. Since alpha-amino acids exist widely in drug molecules and natural products, the classical Strecker synthesis method thereof needs to use toxic cyanide as a carboxyl source, and therefore it is of great application prospect to develop a new method for synthesizing alpha-amino acids by using green CO2 as a carboxyl source. However, so far, the synthesis of alpha-amino acids by using CO2 as a carboxyl source is mainly based on the mechanism of forming a carbon anion intermediate or an alkyl metal species to capture CO2 under the action of photochemistry, electrochemistry, metal chemistry or base promotion, and there are disadvantages such as narrow substrate range and equivalent metal as a reducing agent, and therefore it is urgent to develop a mild and efficient synthesis method. SUMMARY

[0004] In view of the above problems in the prior art, the application provides an N-amino-alpha-amino acid compound and a synthesis method thereof. The synthesis method is based on the carboxylation reaction of hydrazone, and the synthesis method can synthesize important N-amino-alpha-amino acid compounds under mild reaction conditions. The method has the characteristics of mild reaction conditions, wide application range of reaction substrates, good chemical selectivity and cheap and easily available raw materials. The synthesis method can effectively solve the problems in the prior art, such as the limitation of synthesizing alpha-aryl-substituted alpha-amino acid products and the need to use metal reducing agents.

[0005] To achieve the above object, the technical scheme adopted by the application to solve its technical problems is:

[0006] The application discloses a synthesis method of N-amino-alpha-amino acid compounds, which comprises the following steps: adding a reaction substrate, a photocatalyst, a reducing agent and a base into a reaction container, then adding an organic solvent under a CO2 atmosphere, stirring the reaction at 20-70 DEG C under light for 0.1-48 h, and then separating and purifying the reaction product to obtain the N-amino-alpha-amino acid compounds.

[0007] The structural general formula of the reaction substrate is shown in formula (I):

[0008]

[0009] wherein, R 1 , R 2 are hydrogen atoms, all-carbon alkyl, heteroatom-containing alkyl, aryl or trifluoromethyl; R 3 is a hydrogen atom or all-carbon alkyl; R 4 is tert-butyloxycarbonyl, benzyloxycarbonyl, phenyl, benzoyl or sulfonyl.

[0010] Further, the molar ratio of the reaction substrate, the photocatalyst, the solid reducing agent and the base is 1: (0.001-0.01): (1-3.5): (0.5-3).

[0011] Further, the structural general formula of the reaction substrate is as follows:

[0012]

[0013]

[0014] Further, the photocatalyst is a D-A type photocatalyst or an organic metal photocatalyst.

[0015] Further, the reducing agent comprises at least one of formate, organic amine, silane and sulfen.

[0016] Further, the formate is lithium formate, potassium formate, sodium formate or cesium formate.

[0017] The organic amine comprises diisopropylethylamine, triethylamine, triethyl alcohol amine, dicyclohexylmethylamine, dicyclohexyl ethylamine, 1,8-diazabicyclo[5.4.0]undec-7-ene or 1-phenyl-3-methyl-5-pyrazolone.

[0018] Further, the organic solvent comprises at least one of MeCN, DMF, DMAc, DMSO and NMP.

[0019] Further, the base comprises at least one of carbonate, bicarbonate, fluorinated salt, alkoxy base, phosphate, hydrogen phosphate, carboxylate and organic base.

[0020] Further, the reaction pressure in the reaction container is 0.1-30 times of atmospheric pressure, the wavelength of the light source is 300-560 nm, the power of the light source is 1-100 W, and the distance between the light source and the reaction container is 0.1-10 cm.

[0021] An N-amino-alpha-amino acid compound is prepared by the above method.

[0022] The present application has the following beneficial effects:

[0023] 1. The N-amino-alpha-amino acid compound in the present application is prepared by using a readily available hydrazone as a reaction substrate under the catalysis of visible light, CO2 as a carboxylic acid source, and adding a photocatalyst, a reducing agent and a base simultaneously. The method has the characteristics of mild reaction conditions, wide application range of reaction substrates, good chemical selectivity and cheap and readily available raw materials.

[0024] 2. The synthesis method provided by the present application has good reactivity for aromatic hydrazones and aliphatic hydrazones, has the advantage of wide application range of reaction substrates, and has a high yield of products under the use of specific reagents.

[0025] 3. The present application first realizes the carboxylation reaction of hydrazones under visible light catalysis, which efficiently realizes the synthesis of N-amino-alpha-amino acid compounds under mild conditions, and the products are easy to derive and have wide application prospects. BRIEF DESCRIPTION OF DRAWINGS

[0026] Figure 1 The reaction mechanism diagram of the present application. DETAILED DESCRIPTION

[0027] In order to make the purpose, technical scheme and advantages of the present application clearer, the present application will be further described in detail below in combination with examples. It should be understood that the specific examples described herein are only used to explain the present application and are not used to limit the present application, that is, the described examples are only a part of the examples of the present application, but not all the examples.

[0028] Example 1

[0029] A synthesis method of an N-amino-alpha-amino acid compound, when the reaction substrate is , the synthesis reaction formula is shown as formula (1-1), and specifically is:

[0030]

[0031] The synthesis method comprises the following steps:

[0032] After the 10 ml Schlenk reactor equipped with a stirrer was dried by heating under vacuum, the reaction substrate hydrazone compound (0.2 mmol, 1.0 eq.) and the photocatalyst 3DPAFIPN-tBu (1.9 mg, 0.002 mmol, 1.0 mol%) were added, then the reactor was moved into the glove box, the base Cs2CO3 (65.0 mg, 0.2 mmol, 1.0 eq.) was added, then the reactor was sealed with a corresponding stopcock, taken out of the glove box, and replaced with a CO2 atmosphere using double-tube pumping for 3 times, then the reaction substrate hydrazone compound, the polysilane PMHS (30 μL, 0.5 mmol, 2.5 eq.), and super-dry DMSO (1 mL or 2 mL) were added to the reactor under a CO2 atmosphere, the reactor was immediately sealed after the addition was completed, the reactor was fixed in an oil bath (the oil bath was preheated to 60 °C), the stirring speed of the reactor was adjusted to 800-1300 r / min, a 30 W blue LED lamp (wavelength of about 420-480 nm) was used to irradiate at a distance of 0.5 cm, and a fan was used for cooling, so that the reaction temperature was maintained at 60 °C, after stirring for 12 hours, 2.5 mL of ethyl acetate was added to dilute the reaction mixture, 2 mL of 2N hydrochloric acid was added, and stirred for 10 minutes, then the reaction solution was extracted with 2.5 mL of ethyl acetate until no product remained as monitored by thin layer chromatography, the organic phase was combined and the residual solvent was removed by rotary evaporation, the obtained crude product was separated and purified by column chromatography, the purification conditions were as follows: the mixed solvent of petroleum ether: ethyl acetate = 10:1 ~ 5:1 (v:v) was used to remove impurities, and the mixed solvent of petroleum ether: ethyl acetate: glacial acetic acid = 5:1:0.1% ~ 1:2:0.5% (v:v) was used to obtain the target product. The specific reaction product and the corresponding product separation yield results are as follows:

[0033]

[0034]

[0035] In the above results, the data marked a in the upper right corner of the separation yield is the data when the organic solvent is replaced with 2 ml of DMSO, and the other reaction conditions remain unchanged.

[0036] The above experimental results show that the current method is suitable for non-cyclic aliphatic hydrazones, cyclic aliphatic hydrazones, aliphatic aldehyde hydrazones, and can obtain the target product with good yield, and is also suitable for aromatic hydrazone substrates. In addition, functional groups such as alkenyl and trifluoromethyl can be well compatible in the reaction, and the reaction of hydrazones with large steric hindrance is good.

[0037] Based on the above description, for those skilled in the art, the reaction substrate meeting the above reaction mechanism conditions is also suitable, and specifically, when the reaction substrate is replaced by other reaction substrates described in the present application, the remaining components and reaction conditions remain unchanged, and the final yield has little change compared with the yield of the technical scheme of the present application. The applicant will not separately list examples for explanation.

[0038] Example 2

[0039] On the basis of keeping the operation process of Example 1 unchanged, the tert-butyloxycarbonyl-protected 2-tridecanone hydrazone was used as the reaction substrate, and by changing the reaction conditions, the influence of various factors on the reaction yield was investigated. The reaction conditions were as follows: substrate (0.2 mmol, 1 eq.), 3DPAFIPN- t Bu (0.02 mmol, 1.0 mol%, 1.9 mg), PMHS (0.5 mmol, 30 μL, 2.5 eq.), Cs2CO3(0.2 mmol, 65.0 mg, 1.0 eq.), super dry solvent DMSO (2 mL), and the specific experimental results are shown in the following table:

[0040] The reaction process is as follows:

[0041]

[0042] Table: Product yield under different reaction conditions with tert-butyloxycarbonyl-protected 2-tridecanone hydrazone as the reaction substrate

[0043]

[0044]

[0045] As shown by the data in the above table, the yield under the reaction conditions of the present application is as high as 86%. A series of control experiments show that light, photocatalyst, CO2, and reducing agent play an indispensable role in the reaction, and the absence of any of them cannot obtain or can only obtain trace amounts of the target product. When other types of photocatalysts, bases, and organic solvents are used, the yield is greatly reduced, mainly because the remaining raw materials increase. The reason why the product can be detected under a nitrogen atmosphere is that the carbonate decomposes to produce CO2 as the source of the carboxyl group in the presence of protons. In the absence of 3DPAFIPN- t Bu, a certain amount of product can still be produced, and it is speculated that the reason may be that the hydrazone reaction substrate can play the role of a photocatalyst under alkaline conditions, promoting the forward reaction; temperature has a greater influence on the reaction. Using cesium formate instead of polysilane and CO2, the target product can also be obtained in good yield, and according to the mechanism shown in the figure, CO2 and silane can generate formate intermediates in situ, which confirms the rationality of this result.

[0046] Based on the above description, for those skilled in the art, the reaction photocatalyst, reducing agent, base and organic solvent that meet the above reaction mechanism conditions are all qualified, specifically, when the photocatalyst, reducing agent, base and organic solvent are replaced by other types described in the present application, the rest of the ingredients and reaction conditions remain unchanged, and the final yield has little change compared to the yield of the technical solution of the present application. The applicant will no longer explain the examples separately.

[0047] In addition, based on the results of existing experimental research, the inventors propose a reaction mechanism, as shown in Figure 1 First, the substrate hydrazone containing N-H bond generates a nitrogen negative ion intermediate under alkaline conditions, and then undergoes a single electron transfer (SET) process with the excited state photosensitizer to obtain a reduced state photosensitizer and a nitrogen radical intermediate. On the other hand, the polysilane in the system generates formate salt intermediate in situ under alkaline conditions, and the hydrogen atom of the formate salt is captured by the nitrogen radical species to generate CO2 radical anion species and substrate hydrazone, and then the CO2 radical anion attacks the carbon-nitrogen double bond of the hydrazone to generate a new nitrogen radical species, which is reduced to a nitrogen negative ion by single electron transfer (SET) with the reduced state photosensitizer, and finally the target product is obtained by acidification treatment.

[0048] The product prepared by the present application was characterized and analyzed by nuclear magnetic resonance and mass spectrometry. The nuclear magnetic resonance and mass spectrometry characterization data are consistent with the obtained product. The specific characterization data are as follows:

[0049] 2-(2-tert-butoxycarbonylhydrazino)-2-methyltridecanoic acid

[0050]

[0051] 1 H NMR (400 MHz, DMSO-d6) δ 7.71 (s, 1H), 1.38 (s, 11H), 1.24 (s, 18H), 1.10 (s, 3H), 0.90-0.81 (m, 3H). 13 C NMR (101 MHz, DMSO-d6) δ 176.84, 156.94, 78.83, 64.09, 36.70, 31.79, 29.98, 29.53, 29.49, 29.42, 29.20, 28.54, 23.81, 22.57, 21.31, 14.37. HRMS (ESI-): calcd for C 19 H 37 N2O4 - [M-H] - : 357.2759, found 357.2761.

[0052] 2-(2-benzyloxycarbonylhydrazinyl)-2-methyltridecanoic acid

[0053] (m, 5H), 5.12 (s, 2H), 1.69 - 1.56 (m, 2H), 1.37 - 1.25 (m, 21H), 0.92 (t, J = 6.7 Hz, 3H). 13 C NMR (101 MHz, Methanol-d4) δ 177.34, 158.23, 136.70, 128.07, 127.79, 127.68, 127.54, 66.37, 64.47, 48.26, 48.05, 47.91, 47.84, 47.63, 47.41, 47.20, 46.99, 36.65, 31.69, 29.73, 29.39, 29.37, 29.30, 29.16, 29.10, 23.44, 22.36, 19.78, 13.09. HRMS (ESI-): calcd for C 22 H 35 N2O4 - [M-H] - : 391.2602, found 391.2605.

[0054] 2-(2-benzyloxycarbonylhydrazinyl)-2-methyltridecanoic acid

[0055] 7.90 - 7.78 (m, 2H), 7.56 - 7.50 (m, 1H), 7.49 - 7.42 (m, 2H), 1.68 - 1.43 (m, 2H), 1.22 (s, 21H), 0.85 (t, J = 6.8 Hz, 3H). 13 C NMR (101 MHz, DMSO-d6) δ 176.09, 168.33, 166.49, 134.73, 133.45, 131.78, 131.66, 128.74, 128.65, 127.91, 127.78, 64.42, 36.98, 31.76, 29.91, 29.52, 29.47, 29.42, 29.18, 24.29, 22.57, 21.89, 14.42. HRMS (ESI-): calcd for C 21 H 33 N2O3 - [M-H] - : 361.2497, found 361.2497.

[0056] 2-(2-benzyloxycarbonylhydrazinyl)-2-methyltridecanoic acid

[0057] 1H), 1.84 - 1.68 (m, 2H), 1.40 (s, 9H), 1.20 (s, 3H). 13 C NMR (101 MHz, DMSO-d6) δ 176.69, 157.08, 142.87, 128.68, 126.06, 79.00, 64.01, 40.62, 40.41, 40.20, 39.99, 39.78, 39.58, 39.37, 30.22, 28.60, 21.62. HRMS (ESI-): calcd for C 16 H 23 N2O4 - [M-H] - : 307.1663, found 307.1661.

[0058] 4-(4-biphenyl)-2-(2-tert-butoxycarbonylhydrazinyl)-2-methylbutanoic acid

[0059] 7.38 - 7.32 (m, 1H), 7.29 (d, J = 8.0 Hz, 2H), 2.79 - 2.67 (m, 1H), 2.63 - 2.53 (m, 1H), 1.91 - 1.70 (m, 2H), 1.41 (s, 9H), 1.21 (s, 3H). 13 C NMR (101 MHz, DMSO-d6) δ 176.66, 157.13, 142.17, 140.59, 138.06, 129.33, 129.31, 127.58, 127.02, 126.94, 79.04, 64.02, 38.50, 29.86, 28.62, 21.65. HRMS (ESI-): calcd for C 22 H 28 N2NaO4 + [M+Na] + : 407.1941, found 407.1938.

[0060] 2-(2-tert-butoxycarbonylhydrazinyl)-4-(4-methoxyphenyl)-2-methylbutanoic acid

[0061] 2.54 (m, 1H), 2.49 - 2.40 (m, 1H), 1.82 - 1.62 (m, 2H), 1.40 (s, 9H), 1.18 (s, 3H). 13C NMR (101 MHz, DMSO-d6) δ 176.77, 157.79, 157.09, 134.69, 129.57, 114.12, 78.99, 64.04, 55.41, 38.90, 29.31, 28.60, 21.60. LRMS (ESI-): calcd for C 17 H 25 N2O4 - [M-H] - : 337.18, found 337.07.

[0062] 2-(2-tert-Butoxycarbonylhydrazinyl)-4-(4-methoxycarbonylphenyl)-2- methylbutanoic acid

[0063]

[0064] 1 H NMR (400 MHz, DMSO-d6) δ 8.01 - 7.72 (m, 3H), 7.42 - 7.29 (m, 2H), 3.83 (s, 3H), 2.85 - 2.71 (m, 1 H), 2.68 - 2.56 (m, 1 H), 1.87 - 1.68 (m, 2H), 1.40 (s, 9H), 1.19 (s, 3H). 13 C NMR (101 MHz, DMSO-d6) δ 176.53, 166.67, 157.12, 148.86, 129.66, 129.1 1, 127.60, 79.06, 63.92, 52.41, 37.82, 30.23, 28.58, 21.67. HRMS (ESI-): calcd for C 18 H 25 N2O6 - [M-H] - : 365.1718, found 365.1717.

[0065] 4-(1,3-benzoxazol-5-yl)-2-(2-tert-butoxycarbonylhydrazinyl)-2- methylbutanoic acid

[0066] 1 H), 2.50 - 2.38 (m, 1 H), 1.83 - 1.56 (m, 2H), 1.40 (s, 9H), 1.17 (s, 3H). 13C NMR (101 MHz, DMSO-d6) δ 175.65, 156.52, 148.05, 147.44, 129.03, 122.37, 114.33, 111.30, 78.59, 64.79, 55.41, 55.37, 28.14, 20.13. HRMS (ESI-): calcd for C 17 H 23 N2O6 - [M-H] - :351.1562, found 351.1558.

[0067] 2-(2-tert-Butoxycarbonylhydrazinyl)-3-(3,4-dimethoxyphenyl)-2-methylbutanoic acid

[0068] (m, 1H), 6.84 - 6.78 (m, 1H), 6.77 - 6.70 (m, 1H), 3.73 (s, 3H), 3.71 (s, 3H), 2.86 - 2.65 (m, 2H), 1.39 (s, 9H), 1.08 (s, 3H). 13 C NMR (101 MHz, DMSO-d6) δ 175.65, 156.52, 148.05, 147.44, 129.03, 122.37, 114.33, 111.30, 78.59, 64.79, 55.41, 55.37, 28.14, 20.13. HRMS (ESI-): calcd for C 17 H 25 N2O6 - [M-H] - :353.1718, found 353.171.

[0069] 2-Benzyl-2-(2-tert-butoxycarbonylhydrazinyl)-3-phenylpropanoic acid

[0070] Methanol-d4) δ 175.99, 157.17, 136.03, 130.26, 127.77, 126.40, 79.80, 68.11, 40.65, 27.28. HRMS (ESI-): calcd for C 21 H 25 N2O4 - [M-H] - :369.1820, found 369.1818.

[0071] 2-(2-tert-Butoxycarbonylhydrazinyl)-2-ethylbutanoic acid

[0072] 1.39 (s, 9 H), 0.80 (t, J = 7.4 Hz, 6 H). 13 C NMR (101 MHz, DMSO-d6) δ 175.87, 157.00, 78.97, 67.67, 28.59, 8.60. HRMS (ESI-): calcd for C 11 H 21 N2O4 - [M-H] - : 245.1507, found 245.1506.

[0073] 2-(2-tert-Butoxycarbonylhydrazino)-2-trifluoromethylbutanoic acid

[0074] 1.39 (s, 9 H), 0.88 (t, J = 7.4 Hz, 3 H). 13 C NMR (101 MHz, DMSO-d6) δ 168.81, 157.07, 125.51 (q, J = 286.9 Hz), 79.59, 69.72 (q, J = 23.9 Hz), 28.48, 22.26, 8.19. 19 F NMR (376 MHz, DMSO-d6) δ -71.74. HRMS (ESI-): calcd for C 10 H 16 F3N2O4 - [M-H] - : 285.1068, found 285.1065.

[0075] 2-(2-tert-Butoxycarbonylhydrazino)-2-methyl 5-hexenoic acid

[0076] 4.94 (m, 2 H), 2.18 - 2.09 (m, 2 H), 1.77 - 1.68 (m, 2 H), 1.47 (s, 9 H), 1.28 (s, 3 H). 13 C NMR (101 MHz, Methanol-d4) δ 177.13, 157.56, 138.08, 113.65, 79.58, 64.21, 35.60, 27.86, 27.26, 19.80. HRMS (ESI-): calcd for C 12 H 21 N2O4 - [M-H] - : 257.1507, found 257.1503.

[0077] 2-(2-tert-butoxycarbonylhydrazinyl)-2-methylpropanoic acid

[0078] 6H). 13 C NMR (101 MHz, DMSO-d6) δ 177.26, 157.02, 78.96, 61.12, 40.60, 40.44, 40.39, 40.23, 40.18, 39.98, 39.77, 39.56, 39.35, 28.57, 23.67. HRMS (ESI-): calcd for C9H 17 N2O4 - [M-H] - : 217.1194, found 217.1198.

[0079] 2-(2-tert-butoxycarbonylhydrazinyl)-2,3-dimethylbutanoic acid

[0080] NMR (101 MHz, DMSO-d6) δ 177.01, 156.90, 78.84, 67.02, 33.49, 28.58, 17.65, 17.46, 16.63. HRMS (ESI-): calcd for C 11 H 21 N2O4 - [M-H] - : 245.1507, found 241.1513.

[0081] 2-(2-tert-butoxycarbonylhydrazinyl)-2-ethyl-3-methylbutanoic acid

[0082] 0.82 (t, J = 7.4 Hz, 3H). 13 C NMR (101 MHz, DMSO-d6) δ 175.79, 157.03, 79.02, 69.84, 40.62, 40.41, 40.21, 40.00, 39.79, 39.58, 39.37, 32.11, 28.60, 25.13, 18.36, 17.43, 8.94. HRMS (ESI-): calcd for C 12 H 23 N2O4 - [M-H] - : 259.1663, found 259.1666.

[0083] 2-(2-tert-butoxycarbonylhydrazinyl)-2-cyclopropylpropanoic acid

[0084] 0.94 (m, 4H), 0.43 - 0.24 (m, 4H). 13 C NMR (101 MHz, DMSO-d6) δ 175.89, 156.59, 78.46, 63.20, 28.12, 18.40, 17.31, 0.86, 0.68. HRMS (ESI-): calcd for C 11 H 19 N2O4 - [M-H] - : 243.1350, found 243.1346.

[0085] 2-(adamantyl)-2-(2-tert-butoxycarbonylhydrazino)propanoic acid

[0086] DMSO-d6) δ 176.01, 157.03, 78.80, 69.90, 40.40, 40.19, 39.99, 39.78, 39.57, 37.72, 37.01, 36.57, 28.58, 28.49, 14.79. HRMS (ESI-): calcd for C 18 H 29 N2O4 - [M-H] - : 337.2133, found 337.2135.

[0087] 2-(2-tert-butoxycarbonylhydrazino)-2-isopropyl-3-methylbutanoic acid

[0088] 6H). 13 C NMR (101 MHz, DMSO-d6) δ 175.48, 156.95, 79.02, 71.75, 30.46, 28.64, 18.68, 17.59. HRMS (ESI-): calcd for C 13 H 15 N2O4 - [M-H] - : 273.1820, found 273.1824.

[0089] 1-(2-tert-butoxycarbonylhydrazino)cyclopentyl-1-carboxylic acid

[0090] 1.38 (s, 9H). 13C NMR (101 MHz, DMSO-d6) δ 177.78, 156.90, 78.94, 72.03, 34.73, 28.56, 24.90. HRMS (ESI-): calcd for C 11 H 19 N2O4 - [M-H] - : 243.1350, found 243.1351.

[0091] 1-(2-tert-butoxycarbonylhydrazinyl)cyclohexyl-1-carboxylic acid

[0092]

[0093] 1 H NMR (400 MHz, DMSO-d6) δ 7.61 (s, 1H), 1.69 (d, J = 9.9 Hz, 4H), 1.50 - 1.40 (m, 2H), 1.38 (s, 9H), 1.27 (d, J = 23.4 Hz, 5H). 13 C NMR (101 MHz, DMSO-d6) δ 176.76, 156.64, 78.86, 63.50, 31.37, 28.58, 25.68, 21.77. HRMS (ESI-): calcd for C 12 H 21 N2O4 - [M-H] - : 257.1507, found 257.1508.

[0094] 1-(2-tert-butoxycarbonylhydrazinyl)cycloheptyl-1-carboxylic acid

[0095] 1.64 - 1.52 (m, 4H), 1.50 - 1.34 (m, 15H). 13 C NMR (101 MHz, DMSO-d6) δ 177.89, 156.74, 78.87, 67.19, 34.24, 30.51, 28.56, 22.83. HRMS (ESI-): calcd for C 13 H 23 N2O4 - [M-H] - : 271.1663, found 271.1669.

[0096] 1-(2-tert-butoxycarbonylhydrazinyl)cyclooctyl-1-carboxylic acid

[0097] 177.51, 157.42, 79.55, 67.58, 48.24, 48.03, 47.88, 47.81, 47.60, 47.39, 47.17, 46.96, 28.62, 27.97, 27.23, 24.78, 21.87. HRMS (ESI-): calcd for C 14 H 25 N2O4 - [M-H] - : 285.1820, found 285.1819.

[0098] 1-(2-tert-Butoxycarbonylhydrazinyl)cyclododecyl-1-carboxylic acid

[0099] 176.45, 156.67, 78.96, 66.66, 28.57, 28.48, 26.57, 26.09, 22.65, 22.24, 18.90. HRMS (ESI-): calcd for C 18 H 33 N2O4 - [M-H] - : 341.2446, found 341.2440.

[0100] 4-(2-tert-Butoxycarbonylhydrazinyl)tetrahydro-2H-pyran-4-carboxylic acid

[0101] 9H). 13 C NMR (101 MHz, DMSO-d6) δ 176.01, 156.67, 78.97, 63.29, 61.05, 31.40, 28.57. HRMS (ESI-): calcd for C 11 H 19 N2O5 - [M-H] - : 259.1299, found 259.1296.

[0102] 1-(tert-Butoxycarbonyl)-4-(2-tert-butoxycarbonylhydrazinyl)piperidin-4-yl-4-carboxylic acid

[0103] 18H). 13 C NMR (101 MHz, DMSO-d6) δ 176.08, 156.62, 154.40, 78.99, 61.75, 30.56, 28.57, 28.55. HRMS (ESI-): calcd for C 16 H 28 N3O6- [M-H] - :358.1984, found 358.1981.

[0104] 1-(2-tert-butoxycarbonylhydrazinyl)-4-phenylcyclohexyl-1-carboxylic acid

[0105] 7.32 - 7.12 (m, 5H), 2.47 (d, J = 8.7 Hz, 1H), 2.14 - 1.95 (m, 2H), 1.86 - 1.64 (m, 3H), 1.39 (s, 12H). 13 C NMR (101 MHz, DMSO-d6) δ 178.01, 174.99, 156.62, 147.77, 147.03, 128.75, 128.68, 127.14, 127.03, 126.35, 126.28, 78.94, 63.82, 62.49, 43.30, 42.98, 32.39, 30.95, 30.79, 28.64, 28.57. HRMS (ESI-): calcd for C 18 H 25 N2O4 - [M-H] - :333.1820, found 333.1818.

[0106] 1-(2-tert-butoxycarbonylhydrazinyl)-2-methylcyclohexyl-1-carboxylic acid

[0107] 1.95 - 1.81 (m, 1H), 1.80 - 1.61 (m, 2H), 1.61 - 1.39 (m, 3H), 1.38 (s, 9H), 1.33 - 1.18 (m, 3H), 0.88 (d, J = 6.9 Hz, 0.43H), 0.79 (d, J = 7.1 Hz, 2.57H). 13 C NMR (101 MHz, DMSO-d6) δ 177.84, 175.91, 156.57, 78.93, 66.63, 36.97, 30.27, 29.20, 28.59, 28.55, 25.67, 21.69, 20.52, 16.38, 16.31. HRMS (ESI-): calcd for C 13 H 23 N2O4 - [M-H] - :271.1663, found 271.1668.

[0108] 2-(2-tert-butoxycarbonylhydrazinyl)-4-phenylbutanoic acid

[0109] (m, 1H), 2.64 - 2.53 (m, 1H), 1.92 - 1.70 (m, 2H), 1.39 (s, 9H). 13 C NMR (101 MHz, DMSO-d6) δ 174.61, 156.77, 142.24, 128.80, 128.73, 126.22, 79.09, 62.29, 32.60, 31.46, 28.60. HRMS (ESI-): calcd for C 15 H 21 N2O4 - [M-H] - : 293.1507, found 293.1509.

[0110] 2-(2-tert-butoxycarbonylhydrazinyl)-3-ethylheptanoic acid

[0111] MHz, DMSO-d6) δ 174.88, 156.75, 78.98, 64.59, 41.61, 29.75, 29.55, 29.47, 29.40, 28.59, 23.23, 22.84, 22.77, 14.41, 14.37, 12.29, 12.02. HRMS (ESI-): calcd for C 14 H 27 N2O4 - [M-H] - : 241.1976, found 241.1971.

[0112] 2-(2-tert-butoxycarbonylhydrazinyl)-2-cyclohexylethananoic acid

[0113] 5H). 13 C NMR (101 MHz, DMSO-d6) δ 174.36, 79.02, 29.32, 29.07, 28.61, 26.37, 26.29. HRMS (ESI-): calcd for C 13 H 23 N2O4 - [M-H] - : 271.1663, found 271.1667.

[0114] 2-(2-benzyloxycarbonylhydrazinyl)butanoic acid

[0115] 5.04 (s, 2H), 3.40 (t, J = 5.9 Hz, 1H), 1.63 - 1.50 (m, 2H), 0.87 (t, J = 7.4 Hz, 3H). 13 C NMR (101 MHz, DMSO-d6) δ 174.47, 157.35, 137.39, 128.82, 128.30, 128.17, 65.94, 63.87, 23.61, 10.19. HRMS (ESI-): calcd for C 12 H 18 N2O4 + [M+H] + : 253.1183, found 253.1179.

[0116] N-tert-Butoxycarbonylaminovaline

[0117] NMR (101 MHz, DMSO-d6) δ 174.37, 156.80, 79.06, 69.00, 29.94, 28.61, 19.24, 19.00. HRMS (ESI + ): calcd for C 10 H 20 N2NaO4 + [M+Na] + : 255.1315, found 255.1307.

[0118] N-benzyloxycarbonylaminovaline

[0119]

[0120] 1 H NMR (400 MHz, DMSO-d6) δ 8.64 (s, 1H), 7.60 - 7.11 (m, 5H), 5.04 (s, 2H), 3.29 - 3.10 (m, 1H), 1.98 - 1.82 (m, 1H), 1.01 - 0.81 (m, 5H). 13 C NMR (101 MHz, DMSO-d6) δ 174.27, 157.33, 137.39, 128.81, 128.29, 128.15, 68.87, 65.92, 29.85, 19.21, 19.05. HRMS (ESI-): calcd for C 13 H 17 N2O4 - [M-H] - : 265.1194, found 265.1190.

[0121] 2-(2-tert-butoxycarbonylhydrazinyl)-3,3-dimethylbutanoic acid

[0122] 79.03, 73.06, 33.80, 28.61, 27.17. HRMS (ESI-): calcd for C 11 H 21 N2O4 - [M-H] - : 245.1507, found 245.1509.

[0123] Although the present application has been described in detail with particular reference to certain embodiments thereof, it should be understood that modifications and alterations can be made thereto without departing from the scope and spirit of the application.

Claims

1. A N- amino -α- The method for synthesizing an amino acid compound according to claim 1 or 2, wherein The method comprises the following steps: adding a reaction substrate, a photocatalyst, a reducing agent and a base into a reaction container, then adding an organic solvent under a CO2 atmosphere, stirring the reaction at 20-70 ℃ under light for 0.1-48 h, and then separating and purifying the reaction product to obtain N -amino α -amino acid compounds; The structural formula of the reaction substrate is as follows: 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 ； The photocatalyst is 3DPAFIPN t Bu, 3DPAFIPN, 4CzIPN; the reducing agent is polymethylhydrosilane PMHS, i Pr2NEt, NCy2NEt, DIPEA, PhMe2SiH; The base is Cs2CO3 or K2CO3. The organic solvent is DMSO.

2. The method of claim 1, wherein the at least one of the plurality of data packets is a data packet of a first type and the at least one of the plurality of data packets is a data packet of a second type. N- amino -α- A method for synthesizing an amino acid compound, characterized by, The molar ratio of the reaction substrate, the photocatalyst, the reducing agent and the base is 1:(0.001-0.01):(1-3.5):(0.5-3).

3. The method of claim 1, wherein the first and second sets of instructions are stored in a memory of the processor. N- amino -α- A method for synthesizing an amino acid compound, characterized by, The reaction pressure in the reaction container is 0.1-30 times of atmospheric pressure, the wavelength of the light source is 300-560 nm, the power of the light source is 1-100 W, and the distance between the light source and the reaction container is 0.1-10 cm.

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